The goal of this proposal is to establish a collaborative research program between laboratories at the Biology Departments of Lehman College (City University of New York), a predominantly minority institution, and of Columbia University, a major research institution in New York City. The main research aim of this project is to study the role of homeobox genes in neuronal differentiations. Homeobox genes of the vertebrate Hox complexes and the insect homeotic complexes (Hox/HOM genes) are expressed within specific anterior-posterior domains of the central nervous system. The expression patterns of Hox genes suggest a combinatorial code whereby different regions of the nervous system are specified by certain combinations of Hox genes. Certain developmental anomalies of the nervous system found in mammals (including humans) can be traced back to Hox genes. These genes code for homeodomain proteins, a family of transcription factors. It is thought that they control the expression of batteries of genes that specify the particular properties of cells. The Hox/HOM genes are conserved in all animals examined thus far. Our knowledge of Hox/HOM gene function at the single-neuron level is presently quite limited. To improve this situation, it is advantageous to have the ability to study the function of these genes in individual, identified neurons whose properties are well known or easy to study. Nine Hox/HOM genes have been cloned and partially characterized in the leech Hirudo medicinalis. These genes are expressed in different but overlapping sets of neurons. Preliminary results in the leech system support the hypothesis that Hox/HOM genes control the establishment of neuronal identities during development. The objective of this proposal is to test this hypothesis in the leech, a system very suitable for the study of the individual features of neurons. This project intends to study whether neurons that express the same Hox/HOM genes share particular characteristics, such as neurotransmitter type, expression of marker molecules, or axonal morphology, and whether the experimental induction of Hox/HOM gene expression can change aspects of the identity of neurons.